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Updated: Jun 2, 2026
18:48
In Vitro and In Vivo Assessment of T, B and Myeloid Cells Suppressive Activity and Humoral Responses from Transplant Recipients
Published on: August 12, 2017
Frontiers in immunosuppression
1The University of Texas Medical School at Houston, Houston, TX, USA. Barry.D.Kahan@uth.tmc.edu
Transplantation Proceedings
|April 14, 2011
Summary
New immunosuppressants show mixed results in kidney transplants. While some improve renal function, they increase rejection and infection risks, highlighting the need for more targeted therapies.
Area of Science:
- Nephrology
- Immunology
- Pharmacology
Background:
- Available immunosuppressants have significant toxicities, prompting research into nephroprotective agents.
- Belatacept, a CTLA-4 and immunoglobulin conjugate, improved renal allograft function but increased rejection and posttransplant lymphoproliferative diseases.
Purpose of the Study:
- To evaluate novel immunosuppressive agents targeting specific T-cell activation pathways to mitigate nephrotoxicity.
- To assess the efficacy and safety of belatacept, sotrastaurin, and tasocitinib in kidney transplantation.
Main Methods:
- Phase III trial of belatacept (CTLA-4 blockade).
- Phase II trials of sotrastaurin (PKC inhibitor) and tasocitinib (Jak3 inhibitor).
- Comparison of novel agents against tacrolimus-based therapy.
Main Results:
- Belatacept improved renal function but not chronic processes, with increased acute rejection and PTLD.
- Sotrastaurin showed limited benefit and increased adverse events.
- Tasocitinib improved renal allograft function but caused Jak 2 inhibition, leading to infections.
Conclusions:
- Targeting specific T-cell signals (e.g., CTLA-4, Jak3) offers potential but requires careful consideration of off-target effects.
- Developing lymphoid-cell-selective agents is crucial for safer and more effective immunosuppression in kidney transplantation.
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